Molecular recognition chemistry in conjunction with the chemistry of transition metal catalysts can lead to synthetic molecules capable of biomimetic action. Synthetic macrocyclic receptors functionalized with transition metal binding sites are under investigation as mimics of metalloenzymes. The long-term objectives of this research are the identification of new catalysts for selective transformations of organic substrates and an understanding of the fundamental requirements for catalysts within a host-guest or molecular recognition system. Results of this research will contribute to both the basic understanding of enzyme catalysis and the serviceable application of synthetic catalysts to the preparation of new biologically active compounds or degradation of naturally-occurring biomolecules. The specific aims of this three-year period are the study of four new catalyst systems--two for the purpose of metal-catalyzed oxidation of organic substrates and two are in the area of dinuclear metal catalysis of amide or ester hydrolysis. Building upon previous work, we will investigate the chemistry of a bipyridine group substituted with two crown ether moieties. Binding of a single diammonium compound or of two amino acid groups to the crown ether binding sites would place the hydrocarbon side chain adjacent an iron or ruthenium catalysts ligated to the bipyridine. Oxidative chemistry of the bound substrate is predicted to occur in a regioselective fashion at a position proximal to the metal catalyst. New macrocyclic nickel complexes will also be studied which bear polyammonium side chains derived from spermine. Association of the spermine polycations to the phosphate backbone of a nucleic acid will deliver a nickel catalyst for oxidative cleavage. In the area of hydrolysis, studies mimicking the proposed mechanism of urease-catalyzed hydrolysis will be performed. A synthetic macrocyclic compound which bears two metal-binding sites in which their internuclear distances and coordination spheres are well-defined will provide information about the use of two metal ions to promote hydrolysis of amides (e.g., peptides), esters (e.g., phosphodiesters) or ureas. Extension to a trinuclear analog might provide an exceptional catalyst for CO2 hydration as a mimic of carbonic anhydrase. These catalysts are artificial in the sense of representing new designs for substrate binding and catalysis and do not structurally model existing enzymes. Nevertheless, they provide a creative route to functional mimicry of enzymes. Pharmacological applications to the chemistry of biogenic amines, cleavage of DNA or RNA, and hydrolysis of peptides is envisioned.